Adolescents and young women have the highest rates of cervical HPV, including infection with the HPV types causing significant morbidity and mortality. Introduction of the FDA-approved quadrivalent vaccine GARDASIL (Merck & Co., NJ) targeting HPV16 and HPV18 (high-risk types present in >65% of cervical cancers), as well as HPV6 and 11 (associated with most genital warts), has the potential to reduce the burden of genital HPV and disease. However, HPV vaccine clinical trials focused exclusively on low-risk women with limited numbers of sexual partners, who were highly compliant with the vaccine schedule; these females were not representative of those most at risk to suffer from HPV-related disease. In fact, Hispanic and African-American women have the highest and second highest incidence rates of cervical cancer in the U.S., respectively, and high mortality rates from cervical cancer. In addition, the association of HPV-related anal and oropharyngeal lesions is an important public health concern, yet few if any vaccine studies in women evaluated anal and/or oral HPV. Subsequent to the approval and release of GARDASIL, we initiated a prospective cohort study of sexually-active inner-city, predominantly Hispanic and African-American adolescent women attending the Mount Sinai Adolescent Health Center (MSAHC), the largest comprehensive adolescent primary care facility in the U.S. To date, this project has enrolled more than 640 sexually active teens. Prevalent HPV infection at enrollment was detected in 54% of cervical, 41% of anal, and 21% of oral specimens, with vaccine types (HPV 6/11, 16 & 18) present in 7%, 7% and 1% of adolescents, respectively. The cross-sectional baseline detection of vaccine HPV types in the cervix was inversely associated with the number of vaccinations. However, there was considerable incident (new) detection of cervical HPV 16/18 infection in the cervix not present at enrollment despite vaccination (HPV16/18 incidence=4.2 per 100 person years); a rate substantially above that reported in the efficacy trials. We propose to address the health disparities of HPV in minority young women and continue our cohort study of high-risk adolescent women participating in an HPV immunization program at MSAHC. We propose to extend the prospective follow-up (with repeated visits every 6 months) to evaluate longer term burden of infection, and increase the sample size to just over 1,400 subjects to improve statistical power. This will allow us to determine risk factors for break-through HPV infections, and integrate a new aim to evaluate psychosocial elements of adolescent development and risk behaviors in high-risk teens. The data obtained from this study will be essential to understanding the real-world impact of HPV vaccination in this group not studied in the large vaccine trials and will provide the biological underpinnings for future HPV and cervical cancer screening practices, as well as estimating the potential impact of vaccine on anal and oropharyngeal HPV infections.